DDW: Agent May Hold Promise for Crohn's Disease

Action Points

Explain to interested patients that, although this study failed to meet its primary endpoint, it did provide evidence of some benefit from an investigational agent for treating Crohn's disease.

Note that this study was published as an abstract and presented orally at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

CHICAGO, June 2 -- An investigational agent that blocks a receptor expressed by T cells that target the intestines improved disease severity in some patients with moderate-to-severe Crohn's disease, a randomized trial showed.

In the 12-week induction phase of phase II/III trial, the highest dose of CCX282-B (Traficet-EN) caused a clinical response in a greater percentage of patients than did placebo (61% versus 47%, P=0.039), according to Satish Keshav, M.D., Ph.D., of John Radcliffe Hospital in Oxford, England.

The experimental drug blocks the CCR9 chemokine receptor, which is expressed by T cells that selectively migrate to the digestive tract.

The trial missed its primary endpoint, which was a clinical response at eight weeks, but James Lewis, M.D., of the University of Pennsylvania in Philadelphia, said "there's certainly plenty of evidence there that one would want to see more trials going forward."

Drugs that work by preventing immune cells from traveling to sites of inflammation might take more time to show a benefit because existing inflammation will not resolve right away, explained Dr. Lewis, who served as a moderator of the session at which the study was presented.

"There's a lot to lead me to think that maybe there's going to be some good here," he said.

Dr. Keshav reported the results of the first phase of a three-part study, consisting of a 12-week randomized induction phase designed to elicit a clinical response, followed by a four-week open-label phase, closed out by a 36-week randomized maintenance phase, in which the ability of the drug to maintain a clinical response is tested against placebo.

Clinical response was defined as a drop of at least 70 points on the index.

The mean age of the patients was 37 and almost all (99%) had previously received treatment for Crohn's disease.

The patients were randomized to placebo or three different dosing regimens of the CCX282-B: 250 mg twice a day, 250 mg daily, or 500 mg daily.

About half of placebo patients had a clinical response by week eight of the study, which Dr. Keshav called "disappointingly high."

The 500-mg daily dose of the investigational agent was the only one to show a benefit versus placebo.

At week 12, the percentage of patients who had a clinical response was significantly greater with CCX282-B.

Significantly more of the patients who received active treatment had a drop of 100 points on the disease severity index (55% versus 40%, P=0.029).

Among patients who underwent colonoscopy at the beginning of the study, the 500-mg dose produced a significantly larger improvement on the Crohn's Disease Endoscopic Index of Severity (P<0.05).

None of the doses, however, induced disease remission.

The effects of the 500-mg dose did not vary by disease location or duration, baseline levels of C-reactive protein, or concomitant use of other Crohn's medications.

Benefits appeared to be the same in the subset of patients who had previous exposure to antitumor necrosis factor agents.

The treatment was safe, with similar numbers of adverse events (60% with CCX282-B versus 63% with placebo) and serious adverse events (9% versus 10%).

There was no evidence of toxicity or global immunosuppression, according to Dr. Keshav.

Dr. Lewis called the results "very thought-provoking."

"There is always concern when a drug misses its primary endpoint," he said, but added, "I think that there's enough of a biologic explanation here for why you might see greater benefit the farther out you go relative to placebo, and that the 12-week data are at least enough to whet your appetite."

Dr. Keshav reported consulting for Abbott, Ferring Pharmaceuticals, Procter & Gamble Pharmaceuticals, and Schering-Plough. He has also served on advisory committees or review panels for ChemoCentryx, maker of Traficet-EN. Three of the study authors are employees of ChemoCentryx.

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